Alamandine: A promising treatment for fibrosis.

Angiotensin (Ang) II, the main active member of the renin angiotensin system (RAS), is essential for the maintenance of cardiovascular homeostasis. However, hyperactivation of the RAS causes fibrotic diseases. Ang II has pro-inflammatory actions, and moreover activates interstitial fibroblasts and/or dysregulates extracellular matrix degradation. The discovery of new RAS pathways has revealed the complexity of this system. Among the RAS peptides, alamandine (ALA, Ala1 Ang 1-7) has been identified in humans, rats, and mice, with protective actions in different pathological conditions. ALA has similar effects to its well-known congener, Ang-(1-7), as a vasodilator, anti-inflammatory, and antifibrotic. Its protective role against cardiovascular diseases is well-reviewed in the literature. However, the protective actions of ALA in fibrotic conditions have been little explored. Therefore, in this article, we review the ability of ALA to modulate the inflammatory process and collagen deposition, to serve as an antioxidant, and to mediate protection against functional disorders. In this scenario, we also explore ALA as a promising therapy for pulmonary fibrosis after COVID-19 infection.

Assessment of Alamandine in Pulmonary Fibrosis and Respiratory Mechanics in Rodents.

INTRODUCTION: Pulmonary fibrosis (PF) is characterized by an accelerated decline in pulmonary function and has limited treatment options. Alamandine (ALA) is a recently described protective peptide of the renin-angiotensin system (RAS) with essential tasks in several conditions. Our group previously demonstrated that ALA is reduced by 365% in the plasma of patients with idiopathic PF, and thus, it is plausible to believe that stimulation of this peptide could represent an important therapeutic target. In this sense, this study investigates the effects of ALA in an experimental model of PF. MATERIALS AND METHODS: Bleomycin (BLM) was administrated in Wistar rats, and these fibrotic animals were treated with ALA for 14 days. Body weight, histology, respiratory, and hemodynamic parameters were analyzed to study the effects of ALA. RESULTS: ALA treatment attenuated the development of fibrosis (P < 0.0001), reduced respiratory system elastance (P < 0.0001), and preserved weight gain (P < 0.0001) in fibrotic animals without affecting the autonomic control of blood pressure and heart rate. CONCLUSION: The data from this study demonstrate the potential of ALA to alleviate pulmonary fibrosis and improve respiratory system mechanics in vivo. The promising results encourage more detailed investigations of the potential of ALA as a future and efficient antifibrotic.

Chronic administration of pharmacological doses of angiotensin 1-7 and iodoangiotensin 1-7 has minimal effects on blood pressure, heart rate, and cognitive function of spontaneously hypertensive rats.

Cardiovascular diseases are the principal cause of death worldwide, with hypertension being the most common cardiovascular disease risk factor. High blood pressure (BP) is also associated with an increased risk of poor cognitive performance and dementia including Alzheimer's disease. Angiotensin 1-7 (Ang 1-7), a product of the renin-angiotensin system (RAS), exhibits central and peripheral actions to reduce BP. Recent data from our lab reveals that the addition of a non-radioactive iodine molecule to the tyrosine in position 4 of Ang 1-7 (iodoAng 1-7) makes it ~1000-fold more potent than Ang 1-7 in competing for the 125 I-Ang 1-7 binding site (Stoyell-Conti et al., 2020). Moreover, the addition of the non-radioactive iodine molecule increases (~4-fold) iodoAng 1-7's ability to bind to the AT1 receptor (AT1R), the primary receptor for Ang II. Preliminary data indicates that iodoAng 1-7 can also compete for the 125 I-Ang IV binding site with a low micromolar IC50. Thus, our aims were to compare the effects of chronic treatment of the Spontaneously Hypertensive Rat (SHR) with iodoAng 1-7 (non-radioactive iodine isotope) and Ang 1-7 on arterial pressure, heart rate, and cognitive function. For this study, male SHRs were divided into three groups and treated with Saline, Ang 1-7, or iodoAng 1-7 administrated subcutaneously using a 28-day osmotic mini pump. Systolic BP was measured non-invasively by the tail-cuff technique. Cognitive function was assessed by Y-Maze test and novel object recognition (NOR) test. We have demonstrated in SHRs that subcutaneous administration of high doses of iodoAng 1-7 prevented the increase in heart rate with age, while Ang 1-7 showed a trend toward preventing the increase in heart rate, possibly by improving baroreflex control of the heart. Conversely, neither Ang 1-7 nor iodoAng 1-7 administered subcutaneously affected BP nor cognitive function.

125I-Angiotensin 1-7 binds to a different site than angiotensin 1-7 in tissue membrane preparations.

PURPOSE: To study the receptor for Angiotensin (Ang) 1-7 using a radioligand (125I-Ang 1-7)-binding assay. For more than a decade, Mas has been viewed as the receptor for Ang 1-7; however, Ang 1-7 binding has not been pharmacologically characterized in tissue membrane preparations. METHODS: Radioligand-binding assays were carried out using tissue membrane preparations using radioiodinated Angiotensin 1-7 (125I-Ang 1-7) to characterize its binding site. Non-radioactive 127I-Ang 1-7 was used to test if the addition of an iodine to the tyrosine4 moiety of Ang 1-7 changes the ability of Ang 1-7 to competitively inhibit 125I-Ang 1-7 binding. RESULTS: 125I-Ang 1-7 binds saturably, with moderately high affinity (10-20 nM) to a binding site in rat liver membranes that is displaceable by 127I-Ang 1-7 at nanomolar concentrations (IC50 = 62 nM) while Ang 1-7 displaces at micromolar concentrations (IC50 = 80 µM) at ~22 °C. This binding was also displaceable by inhibitors of metalloproteases at room temperature. This suggests that 125I-Ang 1-7 binds to MMPs and/or ADAMs as well as other liver membrane elements at ~ 22 °C. However, when 125I-Ang 1-7-binding assays were run at 0-4 °C, the same MMP inhibitors did not effectively compete for 125I-Ang 1-7. CONCLUSIONS: The addition of an iodine molecule to the tyrosine in position 4 of Ang 1-7 drastically changes the binding characteristics of this peptide making it unsuitable for characterization of Ang 1-7 receptors.

Parasympathetic modulation withdrawal improves functional capacity in pulmonary arterial hypertension.

In 15 pulmonary arterial hypertension patients, the relation of functional capacity to their peripheral endothelial function and sympathaovagal modulation was studied by carrying out brachial artery ultrasound and electrocardiogram spectral analysis, respectively. The functional capacity was assessed by cardiopulmonary exercise testing and six-minute walking test. The sympathovagal modulation was correlated with the predicted peak oxygen consumption (peak VO2 %; r = 0.692, P < 0.05), peak O2 pulse (mL/beat; r = 0.661, P < 0.05), VE, minute ventilation, VCO2 carbon dioxide production (VE/VCO2 slope; r=-0.806, P < 0.01) and distance walked predicted (%6MWT; r = 0.694, P < 0.05). Moreover, there were negative correlations between parasympathetic modulation with peak VO2 (r = 0.755, P < 0.01), peak VO2% (r=-0.727, P < 0.01) and peak O2 pulse (r = 0.615, P < 0.05), %6MWT (r=-0.834, P < 0.01). Collectively these correlations indicate that parasympathetic withdrawal is crucial for improving functional capacity. This conclusion is supported by both positive and negative correlations of parasympathetic modulation with the functional capacity parameters. The sympathetic modulation predominance, although increases the cardiovascular risk, is probably crucial to facilitate the bronchodilation and the oxygen uptake.

Neuromuscular electrical stimulation but not photobiomodulation therapy improves cardiovascular parameters of rats with heart failure.

The aim of the present study was to analyze the effect of neuromuscular electrical stimulation (NMES) and photobiomodulation (PBMT) on the cardiovascular parameters, hemodynamic function, arterial baroreflex sensitivity (BRS), and autonomic balance (ANS) of rats with heart failure (HF). Male Wistar rats (220-290 g) were organized into five groups: Sham (n = 6), Control-HF (n = 5), NMES-HF (n = 6), PBMT-HF (n = 6), and NMES + PBMT-HF (n = 6). Myocardial infarction (MI) was induced by left coronary artery ligation. Animals were subjected to an eight-week NMES and PBMT protocol. Statistical analysis included the General Linear Model (GLM) followed by a Bonferroni post-hoc test. Rats of the NMES-HF group showed a higher MI area than the Control-HF (P = 0.003), PBMT-HF (P = 0.002), and NMES + PBMT-HF (P = 0.012) groups. NMES-HF and NMES + PBMT-HF showed higher pulmonary congestion (P = 0.004 and P = 0.02) and lower systolic pressure (P = 0.019 and P = 0.002) than the Sham group. NMES + PBMT-HF showed lower mean arterial pressure (P = 0.02) than the Sham group. Control-HF showed a higher heart rate than the NMES-HF and NMES + PBMT-HF (P = 0.017 and P = 0.013) groups. There was no difference in the BRS and ANS variables between groups. In conclusion, eight-week NMES isolated or associated with PBMT protocol reduced basal heart rate, systolic and mean arterial pressure, without influence on baroreflex sensibility and autonomic control, and no effect of PBMT was seen in rats with HF.

Family History of Hypertension Impairs the Autonomic Balance, but not the Endothelial Function, in Young Soccer Players. / História Familiar de Hipertensão Prejudica o Balanço Autonômico, mas não a Função Endotelial em Jovens Jogadores de Futebol.

Background The family history of hypertension (FHH) imposes consistent risk for diverse chronic diseases that are accompanied by hypertension. Furthermore, the heart rate variability (HRV) and flow-mediated dilation (FMD) are both related to maximal oxygen uptake (VO2max), and are usually impaired during hypertension Objective To compare the autonomic modulation, the endothelial function (EF) and maximum oxygen uptake (VO2max) of young athletes, separated according to their parents' blood pressure (BP) history, in order to study the influence of their genetic background on those parameters. Methods A total of 46 young male soccer players (18±2 years of age) were divided into four groups: 1-normotensive father and mother (FM-N); 2-only father was hypertensive (F-H); 3-only mother was hypertensive (M-H); 4-father and mother were hypertensive (FM-H). Measurements of BP, FMD, HRV and VO2maxwere performed. The significance level adopted in the statistical analysis was 5%. Results The standard deviation of normal RR intervals (SDNN; FM-N=314±185; FM-H=182.4± 57.8), the square root of the mean squared differences in successive RR intervals (RMSSD; FM-N=248±134; FM-H=87±51), the number of interval differences of successive NN intervals greater than 50ms (NN50; FM-N=367±83.4; FM-H=229±55), the ratio derived by dividing NN50 by the total number of NN intervals (pNN50; FM-N=32.4±6.2; FM-H=21.1±5.3) and the high (HF; FM-N=49±8.9; FM-H=35.3±12) and low-frequency (LF; FM-N=50.9±8.9; FM-H=64.6±12) components, in normalized units (%), were significantly lower in the FM-H group than in the FM-N group (p<0.05). On the other hand, the LF/HF ratio (ms2) was significantly higher (p<0.05). We found no significant difference between the groups in VO2maxand FMD (p<0.05). Conclusions In young male soccer players, the FHH plays a potentially role in autonomic balance impairment, especially when both parents are hypertensive, but present no changes in VO2maxand FMD. In this case, there is a decrease in the sympathetic-vagal control, which seems to precede the endothelial damage (Arq Bras Cardiol. 2020; 115(1):52-58).

Impact of angiotensin II type 1 and G-protein-coupled Mas receptor expression on the pulmonary performance of patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a severe interstitial disease with a mean survival of about 2.5-5 years after diagnosis. Its pathophysiology is still a major challenge for science. It is known that angiotensin II (Ang-II) binds AT1 receptor (AT1R) and its overactivation induces fibrosis, inflammation and oxidative stress. In contrast, activation of the Mas receptor (Mas-R) by angiotensin 1-7 opposes the harmful effects induced by Ang-II. Thus, our innovative objective was to analyze, in patients' lung with IPF, the balance between AT1R and Mas-R expression and their possible association with pulmonary spirometric parameters: forced expiratory volume in the first second (FEV1%) and forced vital capacity (FVC%). One cubic centimeter of lung tissue was obtained from IPF patients (n = 6) and from patients without IPF (n = 6) who underwent bronchial carcinoma resection. Receptor expression was quantified using western blot. AT1R expression was significantly higher (34 %) in patients with IPF (P = 0.006), whereas Mas-R was significantly less expressed (54 %) in these patients' lungs (P = 0.046). There was also a positive correlation between Mas-R expression and FEV1% (r = 0.62, P = 0.03) and FVC% (r = 0.58, P = 0.05). Conversely, AT1R expression was negatively correlated with FEV1% (r = 0.80, P = 0.002) and FVC% (r = 0.74, P = 0.006). In conclusion, our results demonstrated an increased expression of AT1R and reduced expression of Mas-R in the lung of patients with IPF. The dominance of AT1R expression is associated with reduced lung function, highlighting the role of the renin-angiotensin system peptides in the pathophysiology of IPF.

História Familiar de Hipertensão Prejudica o Balanço Autonômico, mas não a Função Endotelial em Jovens Jogadores de Futebol / Family History of Hypertension Impairs the Autonomic Balance, but not the Endothelial Function, in Young Soccer Players

Resumo Fundamento A história familiar de hipertensão (HFH) é um fator de risco consistente para diversas doenças crônicas que são acompanhadas por hipertensão. Além disso, a variabilidade da frequência cardíaca (VFC) e a vasodilatação mediada pelo fluxo (VMF), ambas relacionadas ao consumo máximo de oxigênio (VO2max), são geralmente prejudicadas durante a hipertensão. Objetivo Comparar a modulação autonômica, a função endotelial (FE) e o consumo máximo de oxigênio (VO2max) de jovens atletas, separados de acordo com a história de pressão arterial (PA) dos seus pais, a fim de investigar a influência da ascendência genética nesses parâmetros. Métodos Quarenta e seis jovens jogadores de futebol do sexo masculino (18±2 anos) foram divididos em quatro grupos: 1- pai e mãe normotensos (FM-N); 2- apenas pai hipertenso (F-H); 3- apenas mãe hipertensa (M-H); 4- pai e mãe hipertensos (FM-H). Foram realizadas medições da PA, VMF, VFC e do VO2max. Na análise estatística, foi adotado o nível de significância de 5%. Resultados O desvio padrão dos intervalos RR normais (SDNN; FM-N=314±185; FM-H=182,4± 57,8), a raiz quadrada das médias quadráticas das diferenças dos intervalos R-R sucessivos (RMSSD; FM-N=248±134; FM-H=87±51), o número de diferenças entre intervalos NN sucessivos maiores que 50 ms (NN50; FM-N=367±83,4; FM-H=229±55), a proporção de NN50 dividida pelo número total de NNs (pNN50; FM-N=32,4±6,2; FM-H=21,1±5,3) e os componentes de alta (HF; FM-N=49±8,9; FM-H=35,3±12) e baixa frequência (LF; FM-N=50,9±8,9; FM-H=64,6±12), em unidades normalizadas (%), foram significativamente mais baixos no grupo FM-H do que no grupo FM-N (p<0,05). Por outro lado, a relação LF/HF (ms2) foi significativamente maior (p<0,05). Não foram encontradas diferenças significativas no VO2max e na VMF entre os grupos (p<0,05). Conclusão Em jovens jogadores de futebol do sexo masculino, a HFH desempenha um papel potencialmente importante no comprometimento do balanço autonômico, principalmente quando ambos os pais são hipertensos, mas não apresentam alterações no VO2max e na VMF. Nesse caso, há uma diminuição no controle simpatovagal, que parece preceder o dano endotelial. (Arq Bras Cardiol. 2020; 115(1):52-58)

Abstract Background The family history of hypertension (FHH) imposes consistent risk for diverse chronic diseases that are accompanied by hypertension. Furthermore, the heart rate variability (HRV) and flow-mediated dilation (FMD) are both related to maximal oxygen uptake (VO2max), and are usually impaired during hypertension Objective To compare the autonomic modulation, the endothelial function (EF) and maximum oxygen uptake (VO2max) of young athletes, separated according to their parents' blood pressure (BP) history, in order to study the influence of their genetic background on those parameters. Methods A total of 46 young male soccer players (18±2 years of age) were divided into four groups: 1-normotensive father and mother (FM-N); 2-only father was hypertensive (F-H); 3-only mother was hypertensive (M-H); 4-father and mother were hypertensive (FM-H). Measurements of BP, FMD, HRV and VO2maxwere performed. The significance level adopted in the statistical analysis was 5%. Results The standard deviation of normal RR intervals (SDNN; FM-N=314±185; FM-H=182.4± 57.8), the square root of the mean squared differences in successive RR intervals (RMSSD; FM-N=248±134; FM-H=87±51), the number of interval differences of successive NN intervals greater than 50ms (NN50; FM-N=367±83.4; FM-H=229±55), the ratio derived by dividing NN50 by the total number of NN intervals (pNN50; FM-N=32.4±6.2; FM-H=21.1±5.3) and the high (HF; FM-N=49±8.9; FM-H=35.3±12) and low-frequency (LF; FM-N=50.9±8.9; FM-H=64.6±12) components, in normalized units (%), were significantly lower in the FM-H group than in the FM-N group (p<0.05). On the other hand, the LF/HF ratio (ms2) was significantly higher (p<0.05). We found no significant difference between the groups in VO2maxand FMD (p<0.05). Conclusions In young male soccer players, the FHH plays a potentially role in autonomic balance impairment, especially when both parents are hypertensive, but present no changes in VO2maxand FMD. In this case, there is a decrease in the sympathetic-vagal control, which seems to precede the endothelial damage (Arq Bras Cardiol. 2020; 115(1):52-58)

Altered Gut Microbiome Profile in Patients With Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is considered a disease of the pulmonary vasculature. Limited progress has been made in preventing or arresting progression of PAH despite extensive efforts. Our previous studies indicated that PAH could be considered a systemic disease since its pathology involves interplay of multiple organs. This, coupled with increasing implication of the gut and its microbiome in chronic diseases, led us to hypothesize that patients with PAH exhibit a distinct gut microbiome that contributes to, and predicts, the disease. Fecal microbiome of 18 type 1 PAH patients (mean pulmonary arterial pressure, 57.4, SD 16.7 mm Hg) and 13 reference subjects were compared by shotgun metagenomics to evaluate this hypothesis. Significant taxonomic and functional changes in microbial communities in the PAH cohort were observed. Pathways for the synthesis of arginine, proline, and ornithine were increased in PAH cohort compared with reference cohort. Additionally, groups of bacterial communities associated with trimethylamine/ trimethylamine N-oxide and purine metabolism were increased in PAH cohort. In contrast, butyrate-and propionate-producing bacteria such as Coprococcus, Butyrivibrio, Lachnospiraceae, Eubacterium, Akkermansia, and Bacteroides were increased in reference cohort. A random forest model predicted PAH from the composition of the gut microbiome with 83% accuracy. Finally, virome analysis showed enrichment of Enterococcal and relative depletion of Lactococcal phages in the PAH cohort. In conclusion, patients with PAH exhibit a unique microbiome profile that has the high predictive potential for PAH. This highlights previously unknown roles of gut bacteria in this disease and could lead to new therapeutic, diagnostic, or management paradigms for PAH.

Spirituality and Religiosity are Associated with Quality of Life in Patients with Lung Disease.

Patients were separated into two groups: (1) non-waiting list (NWL) and (2) waiting list (WL) for the lung transplantation. We found greater levels of the faith and spirituality, in those awaiting transplantation. In the NWL group, higher 'meaning' was associated with higher 'vitality,' 'emotional well-being,' and 'mental health'; higher 'peace' was associated with higher 'mental health.' In the WL group, higher 'peace' was associated with and better 'mental health' and 'emotional well-being.' Regardless of whether patients are lung transplantation candidates or not, spirituality/religiosity may help those with lung diseases cope better with their disease and have better quality of life.

Involvement of Neuroinflammation in the Pathogenesis of Monocrotaline-Induced Pulmonary Hypertension.

Pulmonary hypertension (PH) is a devastating disease and its successful treatment remains to be accomplished despite recent advances in pharmacotherapy. It has been proposed that PH be considered as a systemic disease, rather than primarily a disease of the pulmonary vasculature. Consequently, an investigation of the intricate interplay between multiple organs such as brain, vasculature, and lung in PH could lead to the identification of new targets for its therapy. However, little is known about this interplay. This study was undertaken to examine the concept that altered autonomic-pulmonary communication is important in PH pathophysiology. Therefore, we hypothesize that activation of microglial cells in the paraventricular nucleus of hypothalamus and neuroinflammation is associated with increased sympathetic drive and pulmonary pathophysiology contributing to PH. We utilized the monocrotaline rat model for PH and intracerebroventricular administration of minocycline for inhibition of microglial cells activation to investigate this hypothesis. Hemodynamic, echocardiographic, histological, immunohistochemical, and confocal microscopic techniques assessed cardiac and pulmonary function and microglial cells. Monocrotaline treatment caused cardiac and pulmonary pathophysiology associated with PH. There were also increased activated microglial cells and mRNA for proinflammatory cytokines (IL [interleukin]-1ß, IL-6, and TNF [tumor necrosis factor]-α) in the paraventricular nucleus. Furthermore, increased sympathetic drive and plasma norepinephrine were observed in rats with PH. Intracerebroventricular infusion of minocycline inhibited all these parameters and significantly attenuated PH. These observations implicate a dysfunctional autonomic-lung communication in the development and progression of PH providing new therapeutic targets, such as neuroinflammation, for PH therapy.

Effects of isolated vitamin B6 supplementation on oxidative stress and heart function parameters in experimental hyperhomocysteinemia

Introduction: The purpose of this study was to investigate the effects of isolated vitamin B6 (VB6 ) supplementation on experimental hyperhomocysteinemia (Hhe) induced by homocysteine thiolactone (HcyT). Methods: Fifteen male Wistar rats were divided into three groups according to their treatment. Animals received water and food ad libitum and an intragastric probe was used to administer water for 60 days (groups: CB6, HcyT, and HB6 ). On the 30th day of treatment, two groups were supplemented with VB6 in the drinking water (groups: CB6 and HB6 ). After 60 days of treatment, homocysteine (Hcy), cysteine, and hydrogen peroxide concentration, nuclear factor (erythroid-derived 2)-like 2 (NRF2) and glutathione S-transferase (GST) immunocontent, and superoxide dismutase (SOD), catalase (CAT), and GST activities were measured. Results: The HcyT group showed an increase in Hcy concentration (62%) in relation to the CB6 group. Additionally, GST immunocontent was enhanced (51%) in the HB6 group compared to the HcyT group. Also, SOD activity was lower (17%) in the HB6 group compared to the CB6 group, and CAT activity was higher in the HcyT group (53%) compared to the CB6 group. Ejection fraction (EF) was improved in the HB6 group compared to the HcyT group. E/A ratio was enhanced in the HB6 group compared to the CB6 group. Correlations were found between CAT activity with myocardial performance index (MPI) (r = 0.71; P = 0.06) and E/A ratio (r = 0.6; P = 0.01), and between EF and GST activity (r = 0.62; P = 0.02). Conclusions: These findings indicate that isolated VB6 supplementation may lead to the reduction of Hcy concentration and promotes additional benefits to oxidative stress and heart function parameters (AU)

A single dose of dark chocolate increases parasympathetic modulation and heart rate variability in healthy subjects / Uma única dose de chocolate amargo aumenta a modulação parassimpática e a variabilidade da frequência cardíaca em indivíduos saudáveis

ABSTRACT Objective: The aim of this study was to investigate the acute effect of a single dose of dark chocolate (70% cocoa) on blood pressure and heart rate variability. Methods: Thirty-one healthy subjects (aged 18-25 years; both sexes) were divided into two groups: 10 subjects in the white chocolate (7.4 g) group and 21 in the dark chocolate (10 g) group; measurements were performed at the university's physiology lab. An electrocardiogram measured the sympathovagal balance by spectral and symbolic analysis. Results: A single dose of dark chocolate significantly reduced systolic blood pressure and heart rate. After consuming 10 g of dark chocolate, significant increases were observed for heart rate variability, standard deviation of RR intervals standard deviation of all NN intervals, square root of the mean squared differences between adjacent normal RR intervals root mean square of successive differences, and an increase in the high frequency component in absolute values, representing the parasympathetic modulation. Conclusion: In conclusion the importance of our results lies in the magnitude of the response provoked by a single dose of cocoa. Just 10 g of cocoa triggered a significant increase in parasympathetic modulation and heart rate variability. These combined effects can potentially increase life expectancy because a reduction in heart rate variability is associated with several cardiovascular diseases and higher mortality.

RESUMO Objetivo: O objetivo deste estudo foi investigar o efeito agudo de uma única dose de chocolate amargo (70% cacau) sobre a pressão arterial e a variabilidade da frequência cardíaca. Métodos: Trinta e um indivíduos saudáveis (com idade entre 18-25 anos; ambos os sexos) foram divididos em dois grupos: 10 indivíduos no grupo chocolate branco (7,4 g) e 21 no grupo chocolate amargo (10,0 g); as avaliações foram realizadas no laboratório de fisiologia da Universidade Federal de Ciências da Saúde de Porto Alegre. Resultados: O eletrocardiograma foi realizado para analisar o balanço simpatovagal através da análise espectral e simbólica. Uma única dose de chocolate amargo reduziu significativamente a pressão arterial sistólica e a frequência cardíaca. Depois de consumir 10 g de chocolate amargo, observou-se aumento significativo na variabilidade da frequência cardíaca, o desvio padrão dos intervalos, a raiz quadrada da média do quadrado das diferenças entre os intervalos RR normais adjacentes a raiz quadrada da média da soma dos quadrados das diferenças entre os intervalos NN normais adjacentes e um aumento na componente de alta frequência em valores absolutos, o que representa a modulação parassimpática. Conclusão: Em conclusão, a importância dos resultados aqui apresentados reside na magnitude da resposta provocada por uma dose única de cacau (10 g). Esta provocou um aumento significativo da modulação parassimpática e da variabilidade da frequência cardíaca no coração. Esses efeitos, quando combinados, podem, potencialmente, aumentar a esperança de vida, porque a redução da variabilidade da frequência cardíaca está associada a doenças cardiovasculares e maior mortalidade.

Differently shaped spines increase in the posterodorsal medial amygdala of oxytocin knockout female mice.

The posterodorsal medial amygdala (MePD) is a sexually dimorphic area in the social behavior neural network, with high concentration of oxytocin (OT) receptors. Wild type (WT) and OT knockout (OTKO) females were studied in proestrus, and Golgi-impregnated spines in the MePD were classified. Results show that the OTKO group has increased density of thin, mushroom, and stubby/wide spines when compared to the WT (p<0.01 in all cases). These data indicate that OT is an important synaptic modulator in the MePD, a finding that is likely involved with the display of the female sexual behavior.

Efficacy of a low dose of estrogen on antioxidant defenses and heart rate variability.

This study tested whether a low dose (40% less than the pharmacological dose of 17-ß estradiol) would be as effective as the pharmacological dose to improve cardiovascular parameters and decrease cardiac oxidative stress. Female Wistar rats (n = 9/group) were divided in three groups: (1) ovariectomized (Ovx), (2) ovariectomized animals treated for 21 days with low dose (LE; 0.2 mg), and (3) high dose (HE; 0.5 mg) 17-ß estradiol subcutaneously. Hemodynamic assessment and spectral analysis for evaluation of autonomic nervous system regulation were performed. Myocardial superoxide dismutase (SOD) and catalase (CAT) activities, redox ratio (GSH/GSSG), total radical-trapping antioxidant potential (TRAP), hydrogen peroxide, and superoxide anion concentrations were measured. HE and LE groups exhibited an improvement in hemodynamic function and heart rate variability. These changes were associated with an increase in the TRAP, GSH/GSSG, SOD, and CAT. A decrease in hydrogen peroxide and superoxide anion was also observed in the treated estrogen groups as compared to the Ovx group. Our results indicate that a low dose of estrogen is just as effective as a high dose into promoting cardiovascular function and reducing oxidative stress, thereby supporting the approach of using low dose of estrogen in clinical settings to minimize the risks associated with estrogen therapy.

Higher mean blood pressure is associated with autonomic imbalance but not with endothelial dysfunction in young soccer players.

BACKGROUND: Blood pressure (BP) should be kept within a narrow range to allow adequate tissue perfusion. In particular, heart-rate variability (HRV) can be used to assess autonomic cardiovascular modulation, and flow-mediated dilation (FMD) can provide valuable information about the ability of the cardiovascular system to adapt to different pressures. Our objective in the study described here was to investigate the effect of a difference of 10mm Hg in mean arterial pressure (MAP) on endothelial function and autonomic balance in young and normotensive soccer players. METHODS: Twenty-nine young male soccer players (mean age 17.7 years) were divided into two groups according to their MAP (mm Hg): MAP-84 and MAP-94. The BP, FMD, HRV and maximum oxygen uptake (VO2max) of each group were measured. RESULTS: Systolic BP (SBP) and diastolic BP (DBP) were significantly higher (P < 0.0001 and P < 0.006, respectively) in the MAP-94 group. There were no differences in VO2max and endothelial function in the two groups (P < 0.7699). However, the standard deviation (SD) of normal RR intervals (SDNN) and the square root of the mean squared differences in successive RR intervals (RMSSD) were significantly lower in the MAP-94 than in the MAP-84 group (P < 0.0001 and P < 0.005, respectively). In the MAP-94 group, both the high-and low-frequency components were significantly (P < 0.001, P < 0.021, P < 0.017, respectively) lower in both absolute and normalized units, whereas the LF/HF ratio was significantly (P < 0.012) higher. CONCLUSIONS: Collectively, our findings indicate that in young soccer players, autonomic cardiovascular modulation is impaired when MAP is increased by 10mm Hg, even within an optimal range of BP and regardless of endothelial function and VO2max.